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Diffuse intermediate lymphocytic lymphoma. A clinicopathologic study and comparison with small lymphocytic lymphoma and diffuse small cleaved cell lymphoma.

Controversy has recently arisen as to whether diffuse intermediate lymphocytic lymphoma (ILL) should be considered a low-grade or an intermediate-grade non-Hodgkin's lymphoma for clinical purposes. Therefore, the authors performed a clinicopathologic study to determine the biologic course of diffuse ILL (40 cases) and compared it with small lymphocytic lymphoma (SLL; 51 cases) and diffuse small cleaved cell lymphoma (DSCCL; 14 cases). They found that patients with diffuse ILL having pseudofollicular proliferation centers (PC) had a significantly longer median survival (84 months) than those without PC (46.5 months; P = 0.03). The median survival of patients with SLL was 72 months, whereas those with DSCCL had a median survival of only 18 months. Based on these findings, the authors conclude that diffuse ILL with PC should be included in the low-grade category of SLL for clinical purposes, whereas diffuse ILL without PC (true diffuse ILL) should be considered an intermediate-grade non-Hodgkin's lymphoma. True diffuse ILL is similar to centrocytic lymphoma in the Kiel classification and should be accorded a similar status in a modified Working Formulation.

Adult↗

Quantization of accumulated diffused errors in error diffusion.

Due to its high image quality and moderate computational complexity, error diffusion is a popular halftoning algorithm for use with inkjet printers. However, error diffusion is an inherently serial algorithm that requires buffering a full row of accumulated diffused error (ADE) samples. For the best performance when the algorithm is implemented in hardware, the ADE data should be stored on the chip on which the error diffusion algorithm is implemented. However, this may result in an unacceptable hardware cost. In this paper, we examine the use of quantization of the ADE to reduce the amount of data that must be stored. We consider both uniform and nonuniform quantizers. For the nonuniform quantizers, we build on the concept of tone-dependency in error diffusion, by proposing several novel feature-dependent quantizers that yield improved image quality at a given bit rate, compared to memoryless quantizers. The optimal design of these quantizers is coupled with the design of the tone-dependent parameters associated with error diffusion. This is done via a combination of the classical Lloyd-Max algorithm and the training framework for tone-dependent error diffusion. Our results show that 4-bit uniform quantization of the ADE yields the same halftone quality as error diffusion without quantization of the ADE. At rates that vary from 2 to 3 bits per pixel, depending on the selectivity of the feature on which the quantizer depends, the feature-dependent quantizers achieve essentially the same quality as 4-bit uniform quantization.

Algorithms↗

Mass and thermal diffusivity algorithms: reduced algorithms for mass and thermal diffusivity determinations.

Mass and thermal diffusivity measurements conducted on Earth are prone to contamination by uncontrollable convective contributions to the overall transport. Previous studies of mass and thermal diffusivities conducted on spacecraft have demonstration the gain in precision, and lower absolute values, resulting from the reduced convective transport possible in a low-gravity environment. We have developed and extensively tested real-time techniques for diffusivity measurements, where several measurements may be obtained on a single sample. This is particularly advantageous for low gravity research were there is limited experiment time. The mass diffusivity methodology uses a cylindrical sample geometry. A radiotracer, initially located at one end of the host is used as the diffusant. The sample is positioned in a concentric isothermal radiation shield with collimation bores located at defined positions along its axis. The intensity of the radiation emitted through the collimators is measured versus time with solid-state detectors and associated energy discrimination electronics. For the mathematical algorithm that we use, only a single pair of collimation bores and detectors are necessary for single temperature measurements. However, by employing a second, offset, pair of collimation holes and radiation detectors, diffusivities can be determined at several temperatures per sample. For thermal diffusivity measurements a disk geometry is used. A heat pulse is applied in the center of the sample and the temperature response of the sample is measured at several locations. Thus, several values of the diffusivity are measured versus time. The exact analytic solution to a heat pulse in the disk geometry leads to a unique heated area and measurement locations. Knowledge of the starting time and duration of he heating pulse is not used in the data evaluation. Thus, this methodology represents an experimentally simpler and more robust scheme.

Journal Article↗

Water diffusion is elevated in widespread regions of normal-appearing white matter in multiple sclerosis and correlates with diffusion in focal lesions.

Pathological changes in the normal-appearing white matter in multiple sclerosis are well recognised, but their relationship to pathology in focal lesions is not well understood. Magnetic resonance diffusion imaging is sensitive to abnormalities in the integrity, size and geometry of water spaces in brain tissue. This study investigated the anatomical distribution of normal-appearing white matter diffusion abnormalities and their relationship to diffusion in focal lesions in multiple sclerosis (MS). The average apparent diffusion coefficient (ADCav) was measured by three-axis echoplanar diffusion imaging in normal-appearing white matter regions and lesions throughout the brain in 40 patients, and in white matter in 14 matched controls. The correlation between the ADCav in normal-appearing white matter and lesions was determined. In controls and patients, diffusion was highest in the corpus callosum. Patients had a higher mean ADCav than controls in widespread regions including the corpus callosum, cerebellar, temporal and occipital normal-appearing white matter. Mean normal-appearing white matter ADCav correlated strongly with mean lesion ADCav (r = 0.67, P < 0.001). This study demonstrates that water diffusion is elevated in widespread areas of normal-appearing white matter in MS, and is correlated with diffusion in lesions. These findings suggest that the pathogenetic mechanisms causing tissue damage in lesions and normal-appearing white matter are at least partly linked.

Adult↗

Diffusion tensor MR imaging of the brain: effect of diffusion weighting on trace and anisotropy measurements.

BACKGROUND AND PURPOSE: In human brain, the relationship between MR signal and b value is complicated by cerebral perfusion, restricted diffusion, anisotropy, cellular membrane permeability, and active cellular transport of water molecules. Our purpose was to evaluate the effect of the number and strength of diffusion-sensitizing gradients on measured isotropic apparent diffusion coefficients (ADCi), fractional anisotropy (FA), and their respective SD in different anatomic locations of the brain. METHODS: Quantitative apparent diffusion coefficients and diffusion anisotropy brain maps were obtained from 10 healthy volunteers by using six different levels of diffusion weighting (b0 = 0, bl = 160, b2 = 320, b3 = 480, b4 = 640, and b5 = 800 s/mm2), applied sequentially in six different directions (Gxx, Gyy, Gzz, Gxy, Gxz, Gyz) and coupled to a single-shot spin-echo echo-planar (2,045/115 [TR/TE]) MR imaging technique. ADCi, FA, eigenvalues (lambda1, lambda2, lamdba3)1 of the principal eigenvectors, and their respective SD were measured from seven different anatomic locations in the brain. Repeated measures analysis of variance was used to evaluate for the existence of significant differences in the average and SD of the calculated ADCi and FA as a function of the number and strength of b values. When a difference existed, the Bonferroni t method was used for paired comparisons of the groups. RESULTS: The measured ADCi was affected by the number and strength of b values (P < .05). The SD of the ADCi was affected by the strength (P < .05) but not the number of b values (P > .05). The measured FA was unaffected by the number and strength of b values (P > .05). The SD was affected by the number and strength of b values (P < .05). CONCLUSION: The number and strength of b values do influence measures of diffusion and anisotropy. Attention to the choice of diffusion sensitization parameters is important in decisions regarding clinical feasibility (acquisition time) and normative measures.

Adult↗

High-b-value diffusion-weighted MR imaging of adult brain: image contrast and apparent diffusion coefficient map features.

BACKGROUND AND PURPOSE: Recent improvements in MR gradient technology allow significant increases in diffusion weighting without prohibitive signal-to-noise degradation. The purpose of our investigation was to establish normative references for the signal intensity characteristics and apparent diffusion coefficient values of the adult brain at high b values. METHODS: Fifty adults underwent diffusion-weighted single-shot spin-echo echo-planar MR imaging. Isotropic diffusion-weighted images were obtained with b values of 0, 1,000, 2,000, 2,500, 3,000, and 3,500 s/mm2. Qualitative assessments were made in multiple regions of interest in gray and white matter. Three apparent diffusion coefficient maps were generated for each of six patients with a 2-point technique at a b value of 0 and at b values of 1,000, 2,000, and 3,000 s/mm2. RESULTS: Increasing b values result in a progressive decrease in the gray to white matter signal intensity ratio. Isointensity between gray and white matter results at b values between 1,000 and 2,000 s/mm2. At b values greater than 2,000, the gray-white pattern reverses relative to the usual b value of 1,000. Apparent diffusion coefficient values were shown to decrease with increasing b values. CONCLUSION: Attention to the reversal of gray-white contrast and the dependence of apparent diffusion coefficient on the b value are important in avoiding erroneous assignment of pathologic abnormalities to normal regions. This study provides the normative data for future diffusion investigations performed at high b values.

Adolescent↗

Appearance of meningiomas on diffusion-weighted images: correlating diffusion constants with histopathologic findings.

BACKGROUND AND PURPOSE: Malignant and atypical meningiomas are prone to recurrence and aggressive growth, which affects treatment planning and prognostication. Investigators have used diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps to compare tumor grade and cellularity with the histopathologic findings of intraaxial primary brain neoplasms. The purpose of this study was to determine whether the signal characteristics of meningiomas on diffusion-weighted images correlate with the average diffusion constant (Dav) from ADC maps and histopathologic findings and whether the Dav can reliably distinguish benign from malignant and atypical meningiomas. METHODS: Seventeen patients (13 women and four men; average age, 55 years) with meningiomas were prospectively studied using routine MR imaging and diffusion-weighted imaging with a single-shot gradient-echo echo-planar pulse sequence (6000/100 [TR/TE]) and b values of 0 and 1000. Signal characteristics on routine MR and diffusion-weighted images were compared with the histopathologic findings after resection by using World Health Organization criteria. Dav values were calculated within the tumor mass from ADC maps before resection. RESULTS: Four meningiomas were malignant or atypical (World Health Organization grades II and III). Dav values were lower than normal brain values (average, 0.52 +/- 0.12 x 10(-5) cm2/s; range, 0.45-0.69 x 10(-5) cm2/s) and were hyperintense on diffusion-weighted images and hypointense on ADC maps. Thirteen meningiomas were benign. Dav values were higher than normal brain values (average, 1.03 +/- 0.29 x 10(-5) cm2/s; range, 0.62-1.8 x 10(-5) cm2/s). On diffusion-weighted images and ADC maps, most were isointense. Five benign meningiomas had very high Dav values, bright signal on ADC maps, and distinct histopathologic findings, including microcysts, necrotic infarct, and organizing intratumoral hemorrhage. The difference in Dav values between malignant and benign meningiomas was statistically significant (P < .00029). CONCLUSION: Albeit a small sample size, meningiomas with low Dav tended to be malignant or highly atypical (P < .00029) whereas meningiomas with the highest Dav had increased water content due to either a specific histologic subtype of meningioma or the presence of associated pathologic abnormality.

Adult↗

Dependence on diffusion time of apparent diffusion tensor of ex vivo calf tongue and heart.

The time dependence of the apparent diffusion tensor of ex vivo calf heart and tongue was measured for diffusion times (tau(d)) between 32 and 810 ms. The results showed evidence of restricted diffusion in the muscle tissues of both organs. In regions where the myofibers are parallel, the largest eigenvalue (lambda(1)) of the diffusion tensor remained the same for all diffusion times measured, while the other eigenvalues (lambda(2), lambda(3)) decreased by 29-36% between tau(d) = 32 ms and tau(d) = 400 ms. In regions where the fibers cross, the lambda(1) also changed, decreasing by 17% between tau(d) = 32 ms and tau(d) = 400 ms. The restricting compartment size and volume fraction were effectively estimated by fitting the time courses of the eigenvalues to a model consisting of a nonrestricted compartment and a cylindrically restricted compartment. To our knowledge, this study is the first demonstrating diffusion time dependence of measured water diffusion tensor in muscular tissue. With improvement in scanning technology, future studies may permit noninvasive, in vivo detection of changes in muscle myoarchitecture due to disease, treatment, and exercise.

Algorithms↗

Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases - a review.

This paper reviews the current applications of diffusion-weighted and diffusion tensor MRI in diseases of the brain white matter. The contribution that diffusion-weighted imaging has made to our understanding of white matter diseases is critically appraised. The quantitative nature of diffusion MRI is one of its major attractions; however, this is offset by the more advanced hardware required to collect diffusion-weighted images reliably, and the more complex processing to produce quantitative parametric diffusion images. With the now common availability of scanners equipped to perform echo-planar imaging, the acquisition of diffusion tensor images is sure to become more widespread and routine.

Alzheimer Disease↗

Observation of anomalous diffusion in excised tissue by characterizing the diffusion-time dependence of the MR signal.

This report introduces a novel method to characterize the diffusion-time dependence of the diffusion-weighted magnetic resonance (MR) signal in biological tissues. The approach utilizes the theory of diffusion in disordered media where two parameters, the random walk dimension and the spectral dimension, describe the evolution of the average propagators obtained from q-space MR experiments. These parameters were estimated, using several schemes, on diffusion MR spectroscopy data obtained from human red blood cell ghosts and nervous tissue autopsy samples. The experiments demonstrated that water diffusion in human tissue is anomalous, where the mean-square displacements vary slower than linearly with diffusion time. These observations are consistent with a fractal microstructure for human tissues. Differences observed between healthy human nervous tissue and glioblastoma samples suggest that the proposed methodology may provide a novel, clinically useful form of diffusion MR contrast.

Algorithms↗

Diffusive sensitivity to muscle architecture: a magnetic resonance diffusion tensor imaging study of the human calf.

The aim of this study was to examine the diffusive properties of adjacent muscles at rest, and to determine the relationship between diffusive and architectural properties, which are task-specific to muscles. The principle, second, and third eigenvalues, trace of the diffusion tensor, and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated by diffusion tensor imaging (DTI). Linear correlations of the calculated parameters to the muscle physiological cross-sectional area (PCSA), which is proportional to maximum muscle force, were performed to ascertain any linear relation between muscle architecture and diffusivity. Images of the left calf were acquired from six healthy male volunteers. Seven muscles were investigated in this study. These comprised the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus, and peroneus longus. All data were presented as the mean and standard error of the mean (SEM). In general, differences in diffusive parameter values occurred primarily between functionally different muscles. A strong correlation was also found between PCSA and the third eigenvalue, e, and FA. A mathematical derivation revealed a linear relationship between PCSA and the third eigenvalue as a result of their dependence on the average radius of all fibers within a single muscle. These findings demonstrated the ability of DTI to differentiate between functionally different muscles in the same region of the body on the basis of their diffusive properties.

Diffusion Magnetic Resonance Imaging↗

Comparison of total lung diffusion capacity and the membrane component of diffusion capacity as determined by physiologic and morphometric techniques.

Morphometric estimates of diffusion capacity have traditionally been calculated for oxygen (DLO2) while physiologic techniques have been used to determine diffusion capacity for carbon monoxide (DLCO). Morphometric estimates of DLCO and Dm were determined for carbon monoxide so that the results can be directly compared to those obtained using physiologic techniques. Multiple gas rebreathing techniques were used to measure total lung diffusion capacity (DLCO), membrane component of diffusion capacity (Dm) and pulmonary capillary blood volume (Vc) in five anesthetized dogs. After the rebreathing measurements were made, the lungs were inflation fixed with glutaraldehyde and subjected to morphometric analysis. The morphometric estimate of diffusion capacity was three times higher than the physiologic estimate. The major components of diffusion capacity, Dm and theta Vc were found to be of approximately equal size when measured physiologically (Dm = 34 and theta Vc = 27 ml X min-1 X mm Hg-1). In contrast, the morphometric estimate of Dm was about six times higher than the morphometric estimate of theta Vc. The widely different ratios of the two major subcomponents of the total lung diffusion capacity as measured by these two different techniques suggest that the same lung function is not being accurately measured by at least one of these two techniques. Differences in results for DLCO cannot be explained by differences in the physiologic state of the animal at the time the measurement was made. Morphometric analysis predicts that Vc is the major term affecting the value of DLCO whereas the physiologic techniques predict that both Dm and Vc contribute substantially to the value of DLCO.

Animals↗

Diffusivity of 125I-labelled macromolecules through collagen: mechanism of diffusion and effect of adsorption.

Diffusion of angiotensin II, albumin and aldolase was studied through collagen membranes with swelling ratios between 4 and 15. The diffusion coefficient was measured from the time-lag for the onset of steady-state flux through the membrane. Binding of macromolecules to collagen was evaluated from the results of sorption studies conducted as a function of macromolecular concentration. Results presented indicate that the diffusion of macromolecules through collagen membrane is slowed by electrostatic and hydrogen bonding between individual macromolecular chains and collagen. The extent of adsorption is increased as the molecular weight of the diffusant increases. Diffusion of water soluble macromolecules through collagen occurs rapidly, suggesting that diffusion occurs through water filled channels as opposed to between collagen molecules. The results of these studies are useful in understanding diffusion through connective tissues and in the design of drug delivery systems based on collagen.

Adsorption↗

Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice.

Diffusion tensor imaging (DTI) using variable diffusion times (t(diff)) was performed to investigate wild-type (wt) mice, myelin-deficient shiverer (shi) mutant mice and shi mice transplanted with wt neural precursor cells that differentiate and function as oligodendrocytes. At t(diff) = 30 ms, the diffusion anisotropy "volume ratio" (VR), diffusion perpendicular to the fibers (lambda( perpendicular)), and mean apparent diffusion coefficient ( ) of the corpus callosum of shi mice were significantly higher than those of wt mice by 12 +/- 2%, 13 +/- 2%, and 10 +/- 1%, respectively; fractional anisotropy (FA) and relative anisotropy (RA) were lower by 10 +/- 1% and 11 +/- 3%, respectively. Diffusion parallel to the fibers (lambda(//)) was not statistically different between shi and wt mice. Normalized T(2)-weighted signal intensities showed obvious differences (27 +/- 4%) between wt and shi mice in the corpus callosum but surprisingly did not detect transplant-derived myelination. In contrast, diffusion anisotropy maps detected transplant-derived myelination in the corpus callosum and its spatial distribution was consistent with the donor-derived myelination determined by immunohistochemical staining. Anisotropy indices (except lambda(//)) in the corpus callosum showed strong t(diff) dependence (30-280 ms), and the differences in lambda( perpendicular) and VR between wt and shi mice became significantly larger at longer t(diff), indicative of improved DTI sensitivity at long t(diff). In contrast, anisotropy indices in the hippocampus showed very weak t(diff) dependence and were not significantly different between wt and shi mice across different t(diff). This study provides insights into the biological signal sources and measurement parameters influencing DTI contrast, which could lead to developing more sensitive techniques for detection of demyelinating diseases.

Algorithms↗

Lateral diffusion coefficients in membranes measured by resonance energy transfer and a new algorithm for diffusion in two dimensions.

We describe measurements of lateral diffusion in membranes using resonance energy transfer. The donor was a rhenium (Re) metal-ligand complex lipid, which displays a donor decay time near 3 micros. The long donor lifetime resulted in an ability to measure lateral diffusion coefficient below 10(-8) cm(2)/s. The donor decay data were analyzed using a new numerical algorithm for calculation of resonance energy transfer for donors and acceptors randomly distributed in two dimensions. An analytical solution to the diffusion equation in two dimensions is not known, so the equation was solved by the relaxation method in Laplace space. This algorithm allows the donor decay in the absence of energy transfer to be multiexponential. The simulations show that mutual lateral diffusion coefficients of the donor and acceptor on the order of 10(-8) cm(2)/s are readily recovered from the frequency-domain data with donor decay times on the microsecond timescale. Importantly, the lateral diffusion coefficients and acceptor concentrations can be recovered independently despite correlation between these parameters. This algorithm was tested and verified using the donor decays of a long lifetime rhenium lipid donor and a Texas red-lipid acceptor. Lateral diffusion coefficients ranged from 4.4 x 10(-9) cm(2)/s in 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG) at 10 degrees C to 1.7 x 10(-7) cm(2)/s in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at 35 degrees C. These results demonstrated the possibility of direct measurements of lateral diffusion coefficients using microsecond decay time luminophores.

Algorithms↗

A mathematical model of diffusion-limited gas bubble dynamics in tissue with varying diffusion region thickness.

The three-region model of gas bubble dynamics consists of a bubble and a well-stirred tissue region with an intervening unperfused diffusion region previously assumed to have constant thickness and uniform gas diffusivity. As a result, the diffusion region gas content remains unchanged as its volume increases with bubble growth, causing dissolved gas in the region to violate Henry's law. Earlier work also neglected the relationship between the varying diffusion region volume and the fixed total tissue volume. The present work corrects these theoretical inconsistencies by postulating a difference in gas diffusivity between an infinitesimally thin layer at the bubble surface and the remainder of the diffusion region, thus allowing both thickness and gas content of the diffusion region to vary during bubble evolution. The corrected model can yield bubble lifetimes considerably longer than those yielded by earlier three-region models, and meets a need for theoretically consistent but relatively simple bubble dynamics models for use in studies of decompression sickness (DCS) in human subjects.

Air Pressure↗

An integrated sorption-diffusion model for the calculation of consistent distribution and diffusion coefficients in compacted bentonite.

A thermodynamic sorption model and a diffusion model based on electric double layer (EDL) theory are integrated to yield a surface chemical model that treats porewater chemistry, surface reactions, and the influence of charged pore walls on diffusing ions in a consistent fashion. The relative contribution of Stern and diffuse layer to the compensation of the permanent surface charge represents a key parameter; it is optimized for the diffusion of Cs in Kunipia-F bentonite, at a dry density of 400 kg/m3. The model is then directly used to predict apparent diffusivities (Da) of Cs, Sr, Cl-, I- and TcO4- and corresponding distribution coefficients (Kd) of Cs and Sr in different bentonites as a function of dry density, without any further adjustment of surface chemical and EDL parameters. Effective diffusivities (De) for Cs, HTO, and TcO4- are also calculated. All calculated values (Da, De, Kd) are fully consistent with each other. A comparison with published, measured data shows that the present model allows a good prediction and consistent explanation of (i) apparent and effective diffusivities for cations, anions, and neutral species in compacted bentonite, and of (ii) Kd values in batch and compacted systems.

Adsorption↗

Influence of ingredients on the self-diffusion of aroma compounds in a model fruit preparation: an nuclear magnetic resonance-diffusion-ordered spectroscopy investigation.

Diffusion-ordered spectroscopy (DOSY)-pulsed field gradient (PGF) nuclear magnetic resonance (NMR) spectroscopy was used to measure self-diffusion coefficients of aroma molecules in model fruit preparations. The impact of the sucrose content on aroma diffusion was specifically investigated, and the relationship with viscosity, water activity, and dry matter parameters was evidenced. DOSY-PGF NMR spectroscopy was found to be a relevant and accurate technique to follow self-diffusion of aroma compounds at low concentrations in a complex food matrix and to obtain information on diffusion of the sucrose and of the water molecules. We showed that aroma self-diffusion was strongly decreased in fruit preparation because of the high sucrose content, which induces the formation of a network through hydrogen bonds with water. Self-diffusion coefficients were determined for aroma molecules of different natures, and values are related to the physicochemical properties of the molecule.

Butyrates↗